Zanamivir is the first neuraminidase inhibitor to be developed commercially, and it is used in the treatment of and prophylaxis of both Influenza virus A and Influenza virus B. Chemically, zanamivir is 5-(acetylamino)-4-[(aminoiminomethyl)amino]-2,6-anhydro-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enonic acid (Formula I), and is represented by the following structure:

Zanamivir binds to the conserved region of influenza neuraminidase enzyme, which mainly catalyzes the cleavage of terminal sialic acid attached to glycolipids and glycoproteins.
The process for preparation of zanamivir was first described in EP 0526543. The synthetic method employed in the patent is depicted in the following reaction Scheme 1:
wherein, selective deacetylation of methyl 5-acetamido-4-acetoxy-6-(1,2,3-triacetoxypropyl)-5,6-dihydro-4H-pyran-2-carboxylate (II) with boron trifluoride ethearate gives methyl 5-acetamido-4-hydroxy-6-(1,2,3-triacetoxypropyl)-5,6-dihydro-4H-pyran-2-carboxylate (III), which on further treatment with trifluoromethanesulfonic anhydride and sodium azide gives methyl 5-acetamido-4-azido-6-(1,2,3-triacetoxypropyl)-5,6-dihydro-4H-pyran-2-carboxylate (IV). The reduction of intermediate compound (IV) with hydrogen sulphide in pyridine affords the corresponding methyl 5-acetamido-4-amino-6-(1,2,3-triacetoxypropyl)-5,6-dihydro-4H-pyran-2-carboxylate intermediate (V), which is finally condensed with S-methylisothiourea in water and saponified through Dowex 50 W×8 in aqueous ammonium hydroxide to yield zanamivir (I). The problems associated with the disclosed process are that even on passing hydrogen sulphide gas for around 16 hours, there is no complete reduction of the 4-azido intermediate into the 4-amino compound. Also, due to the excessive use of the gas, there is a risk of undesired reduction of the 2,3-double bond along with the 4-azido group. The over-reduction leads to formation of undesired products which need additional purification procedures in order to separate the undesired products.
WO 1994/07885 discloses a process for preparing zanamivir, as given in Scheme 2 below, by treating 5-acetamido-4-amino-6-(1,2,3-trihydroxypropyl)-5,6-dihydro-4H-pyran-2-carboxylic acid (VI), obtained from WO 1991/16320, with cyanogen bromide in the presence of sodium acetate to yield 4-cyanoamide derivative (VII) which is further reacted with ammonium formate and ammonia.

AU 672634 discloses the synthesis of zanamivir by reacting the 5-acetamido-4-amino-6-(1,2,3-trihydroxypropyl)-5,6-dihydro-4H-pyran-2-carboxylic acid (VI) with pyrazole-1H-carboxamidine.
EP 0539204 also discloses the preparation of zanamivir by treating cyano derivative (VII) with an amine derivative or treating 4-amino compound (VI) with a carbamimidic compound.
EP 0623121 discloses the use of a Lindlar catalyst (lead doped palladium catalyst) for the conversion of the methyl 5-acetamido-4-azido-2,3-didehydro-2,3,4,5-tetradeoxy-D-glycero-D-galacto-2-nonulopyranosidonate to its methyl 5-acetamido-4-amino-2,3-didehydro-2,3,4,5-tetradeoxy-D-glycero-D-galacto-2-nonulopyranosidonate form. It has been found that recovery of the Lindlar catalyst from the reactant solution requires an expensive procedure, thus making the process expensive. Also, this catalyst has a short lifetime due to poisoning.
One of the intermediates for use in the synthesis of zanamivir is the compound of formula (VI), the synthesis of which has previously been described in the above-mentioned patents either by reducing the azido precursor with a Lindlar catalyst or using hydrogen sulphide gas. These processes generate a lot of undesired impurities due to the harsh reaction conditions which further affect the purity and yield of the product. Hence, there is a need for an alternate process for the synthesis of the compound (VI).
The problems associated with the prior art processes involve the use of a costly catalyst, expensive recovery procedures and high reaction time. Hence, in order to overcome these problems, there is need for an improved or alternate process for preparation of zanamivir that is simple, economical, eco-friendly and industrially scaleable.